Hi, this weekend I bought a Fractal Design Define R4 and lifted over all my gear into it. The image below shows my current fan layout.
The motherboard is an Asus Z68-V GEN3.

Upper drive cage is removed to improve front air intake.

Fans A and B are the 14 cm 3 pin fans that were included in the case. I put them at 7 V since I can hear them at 12 V, but not at 5 or 7 V.

Fan C is the default Cooler Master Hyper 212 EVO fan, in a push configuration. It is connected to CPU FAN header.

Fan D is a Xigmatek XAF 14 cm 4 pin PWM fan. It is connected via a 3-way+Molex splitter and is synced to the CPU fan. (With the current setup I could get the same effect by connecting it to the CPU OPT header, but with fewer cables involved so I might do just that.)

Fans E and F are identical to Fan D. Fan D is connected to CHA1, which is a 4 pin non-PWM header (I think it is voltage controlled, definitely not PWM).

Fan F is connected to CHA2, which is a 3 pin slave of CHA1, so the E & F are always giving the same RPM. I cannot control CHA2 directly, but it must be controlled by CHA1.

There is a side mount and a forward top mount that are not used and has the noise blockers covering the ports.

For the GPU I am using EVGA Precision X, and I am using Asus Fan Xpert 2 to set up a fan profile for the CPU fan and that works effortlessly! The processsor is a i5-2500 at 4.3 GHz. With E&F off I am getting CPU temps of about 45 C in Intel Burn test, and below 40 C in games, which I find quite remarkable, so I really do not need more cooling for the CPU. However the GPU temps are worse, and since I want to replace my old card any day now with an overclocked 7950 that area needs some attention. Also the GPU noise is the loudest of the entire case so keeping the GPU well supplied with cold air is a priority. The idea is to supply the GPU with cold air from F and pulling it out at D&E.

The problem: Fan Xpert 2 cannot create a fan profile as a function of GPU temp, or anything else but CPU temp for that matter. Instead I have E&F synced to CPU temp, where they kick in at 40 C, but since the CPU is so cool that never happens in a real life situation no matter how hot the GPU is. I can set the CHA1 threshold lower than 40 C to make sure they are almost always spinning at low speed, but that is pretty stupid solution since they wont spin up with increasing GPU temp.

Before you suggest it, I have tried Speedfan and it does not report CPU temperature(!), and the individual core temps look completely crazy. That, and that it would not let me actually control the speed of any fan makes me think it is just too far outdated and does not support newer motherboards.

Is there a way to control fans E&F through Fan Xpert 2 or any other software? If that software also can control the GPU fan that would be a very nice bonus!

You could try replacing the fans mentioned with Artic Cooling F12 TC. It isn't the most elegant approach nor is it cheap like a software solution, but with the temp probe, you could sneak it near the GPU where it would ramp up according to the temp of the GPU.

The only problem that might occur is that the probe has a very low temp range as mentioned in the link. You could probably adjust how sensitive the probe is by adjusting its distance from the hottest point or encase the probe with some insulation to make it less sensitive and ramp up only at a higher temp.

Thanks for the advice! I just learned of those fans with sensors, they sound quite useful.

I went to Speedfan and after quite some struggle I managed to link fan E&F to the GPU temperature, and put set a fan profile that steps from 0% to 37% power at 45 C, and from there a smooth increase toward 100% power. Since Speedfan is very dodgy for anything that concerns my CPU I am still using Asus Fan Xpert 2 to control the other fans. So it works!

However, this method of two pieces of software running in parallel, and Speedfans terrible interface is far from optimal, so if there are better alternatives out there I am all ears.

(Now I try to do the same in Linux. Linux runs E&F at a flat 50% rate by default. )

Thanks for the advice! I just learned of those fans with sensors, they sound quite useful.

I went to Speedfan and after quite some struggle I managed to link fan E&F to the GPU temperature, and put set a fan profile that steps from 0% to 37% power at 45 C, and from there a smooth increase toward 100% power. Since Speedfan is very dodgy for anything that concerns my CPU I am still using Asus Fan Xpert 2 to control the other fans. So it works!

However, this method of two pieces of software running in parallel, and Speedfans terrible interface is far from optimal, so if there are better alternatives out there I am all ears.

(Now I try to do the same in Linux. Linux runs E&F at a flat 50% rate by default. )

SpeedFan is without a doubt the best program I know of to do what you want to do, but I agree its setup isn't very intuitive. Here's a few posts I made awhile ago about setting it up: http://forums.anandtech.com/showthread.php?t=2227401 . Basically you want to define your fans' operating parameters, your temperature parameters, and how temperatures control the fans' within their parameters. For example, my system has four fans, all GT AP-15's, all exhaust, two on each of my 240mm radiators. I've set them to run between 40% and 80%. Next I have temperature parameters set for every device in my system that SpeedFan detects, and I have a desired temp (if temps go above this SpeedFan increases my fans from 40% to 80% until temperatures stabilize and drop), as well as a warning temp (if the part hits this temp, SpeedFan kicks all fans on 100%). Each device has full control over the fans (although you can have certain components control certain fans). I also have some "safety" features enabled like turning the fans on 100% incase SpeedFan shuts down accidentally, and some "aesthetic" features like ramping the fans up only 3% at a time. Let me know if any of this doesn't make sense or you would like to see pictures.